Metabolic control mechanisms have been postulated to play a critical role in the autoregulation of the renal circulation and the regulation of renin secretion, but the cellular mechanisms for such effects have not been fully defined. The overall aim of these studies is to characterize the role of three types of membrane proteins which may participate in metabolic coupling of renin secretion and renal blood flow. Most studies will employ the technique of isolated perfused rabbit afferent arterioles, or isolated mouse juxtaglomerular cells. The specific aims of part I is to evaluate the role of ATP-sensitive K channels in regulation of afferent arteriolar tone and renin secretion. Functional studies using pharmacological activators and blockers of these channels will examine their role in renin secretion and afferent arteriolar tone. Studies are also proposed using patch clamp techniques applied to vascular smooth muscle cells and isolated granular cells, and using physiological manipulation of intracellular ATP levels. The specific aim of Part 2 is to evaluate the role of facilitative glucose transporters, particularly GLUT4 in regulation of afferent arteriolar tone and renin secretion. Studies are proposed to assess the factors which regulate mRNA and protein levels for GLUT4 in afferent arterioles and JG granular cells. Studies are also proposed to determine the effect of hypoxia, high and low insulin levels and high and low glucose levels on GLUT4 mRNA and protein levels in JGA using both in vivo and in vitro preparation, and to study effect of variation in glucose transport on renin secretion and afferent tone in vitro. The specific aim of Part 3 is to assess the role of purinergic(P2) receptors on juxtaglomerular and afferent arteriolar cells. Studies are proposed to determine the effect of ATP and ATP analogs on afferent arteriolar tone and renin secretion, to assess whether the endothelium participates or modulates purinergic effects, and to assess whether there is synergism between angiotensin II and ATP-mediated effects.